U T I A.K.

A I S K
BASIC STRUCTURES OF THE URINARY
SYSTEM
The urinary system
consists of:
two kidneys
two ureters
one urinary
bladder
one urethra

FUNCTIONS OF THE BASIC STRUCTURES OF
THE URINARY SYSTEM
Kidney small, dark red kidney bean shaped structures. The kidneys are
responsible for continuously cleansing the blood and adjusting its composition,
urine formation, excretion of Nitrogen containing wastes, maintaining water
and electrolyte balance of the blood, maintaining the acid base balance of
the blood and the formation of urine.
Ureters slender tubes each 10 to 12 inches in long and inch in
diameter. Each ureter runs from the kidney down to the urinary bladder and
attaches itself to the posterior aspect of the bladder on a slight angle. The
ureters are passageways to carry urine from the kidneys to the bladder.
Urinary Bladder is a smooth, collapsible, muscular sac with 3
openings, the 2 ureter openings and the urethra opening. When the bladder is
empty, it is collapsed and it is 2 to 3 inches long at most, when the bladder is
moderately full about 500ml it is about 5 inches long. The bladder is able to
hold twice that amount though. The main function of the urinary bladder is to
provide a temporary storage tank for urine.
Urethra is a thin walled tube that carries urine by peristalsis from the
bladder to the outside of the body. The length and relative function of the
urethra differs in both sexes.
FUNCTIONS OF THE URINARY SYSTEM
The principal function of the urinary system is to maintain the volume
and composition of body fluids within normal limits. One aspect of this
function is to rid the body of waste products that accumulate as a result
of cellular metabolism.
The urinary system maintains an appropriate fluid volume by regulating
the amount of water that is excreted in the urine. Other aspects of its
function include regulating the concentrations of various electrolytes in
the body fluids and maintaining normal pH of the blood
In addition to maintaining fluid homeostasis in the body, the urinary
system controls red blood cell production by secreting the hormone
erythropoietin. The urinary system also plays a role in maintaining
normal blood pressure by secreting the enzyme renin.


DIFFERENCES BETWEEN THE MALE AND
FEMALE URINARY SYSTEM
Male
Urethra
Female
Urethra
Approx 8
inches long
Approx 1.5
inches long
Located
further from
anus
Located more
proximate to
anus
Has two
functions,
urination &
passageway
for sperm
Has one
function,
urination
OVERVIEW OF UTI
7 million office visits yearly
1 million hospitalizations
About 2/3rds of patients are women; 40%
to 50% of women have UTI at some point
during their lives
Important complications of pregnancy,
diabetes mellitus, polycystic disease, renal
transplantation, conditions that impede
urine flow (structural and neurologic)
OVERVIEW OF UTI BY AGE AND SEX
TERMS (1)
UTI: the finding of microorganisms in
bladder urine with or without clinical
symptoms and with or without renal
disease
Significant bacteriuria: the finding of >
10
5
cfu/ml of urine (but lower counts can
be significant)
SYMPTOMS VERSUS ASYMPTOMATIC
BACTERIURIA
Asymptomatic Bacteriuria (ASB)
Defined as the presence of bacteria in
urine of patients who do not have dysuria,
urinary frequency, urgency, fever, flank
pain, or other symptoms related to
irritation of the urethra, bladder, or kidney
Swart, Soler & Holman, 2004
Strictly definedexists when 2 urine
cultures done with clean-catch specimens
are positive in a patient who has no
urinary tract symptoms
Foxman, 2003
TERMS (2)
Asymptomatic bacteriuria: Significant
bacteriuria without clinical symptoms or
other abnormal findings.
Acute bacterial pyelonephritis: a clinical
syndrome of fever, flank pain, and
tenderness, often with constitutional
symptoms, leukocyte casts in the urine,
and bacteriuria; or histologic findings
thereof
TERMS (3)
Chronic bacterial pyelonephritis: Long-
standing infection associated with active
bacterial growth in the kidney; or the
residuum of lesions caused by such infection
in the past
Chronic interstitial nephritis: renal disease
with histologic findings resembling chronic
bacterial pyelonephritis but without evidence
of infection
TERMS (4)
Upper UTI: infection above the level of the
bladder
Lower UTI: infection at or below the level of
the bladder
Urethral syndrome: clinical manifestations
of lower UTI (dysuria, frequency, urgency)
without significant bacteriuria
TERMS (5)
Pyuria: the presence of pus
(WBCs [leukocytes] in urine,
which may or may not be caused
by UTI. The preferred method for
quantitation is enumeration in
unspun urine using a counting
chamber. The leukocyte esterase
nitrite test has a sensitivity of
between 70% and 90% for
symptomatic UTI
Recurrent UTIsculture-confirmed UTIs
* >3 in 1 year or
* > 2 in 6 months

Relapse UTI occurs within 2 weeks of Rx
of an earlier UTI
same pathogen
Re-infection UTI occurs >4 weeks after
earlier UTI
different pathogen

Swart, Soler & Holman, 2004

RISK FACTORS IN UTIS
Females
Sexual intercourse
poor fitting diaphragms
use of spericide
Pregnancy/Menopause
Clothing
tight jeans
wet bathing suits
pantyhose
synthetic underwear
Allergens/Irritants
feminine hygiene sprays
bubble baths
perfumed toilet paper / soap
sanitary napkins
Presence of indwelling catheter
Foley

Males
Age
Loss of bactericidal properties
of prostatic secretions
sperm
Obstructive Uropathy
BPH
Presence of indwelling
catheter
Foley
ASYMPTOMATIC BACTERIURIA
In patients with asymptomatic
bacteriuria without infection, a colony
count of > 10
5
cfu/ml defines infection
Screening has little apparent value in
adults except during pregnancy and
prior to urologic surgery
Up to 40% of elderly men and women
have asymptomatic bacteriuria

FREQUENCY OF SIGNIFICANT BACTERIURIA (1)
After one bladder catheterization: 2%
Medical outpatients: 5%
Pregnancy at term: 10%
Hypertensive patients: 14%
Diabetes mellitus: 20%
Women with cystocoele: 23%
FREQUENCY OF SIGNIFICANT BACTERIURIA (2)
Congenital urologic disease: 57%
Hydronephrosis; nephrolithiasis: 85%
Indwelling catheter, open drainage > 48
hours: 98%
(reference: Jackson et al, Arch Intern Med
1962; 110: 663)
SCREENING FOR SIGNIFICANT BACTERIURIA
Screening for asymptomatic bacteriuria
in adults has little value except for two
situations: pregnancy (because of the
high risk of acute pyelonephritis with its
accompanying risk of fetal
complications) and prior to urologic
surgery (because of the risk of
postoperative sepsis).
URINARY TRACT BACTERIOLOGY
At room temperature, the doubling time of
common aerobic bacteria is about 20
minutes
Some contaminants in voided urine:
Lactobacilli, Cornyebacterium species,
Gardnerella, alpha-hemolytic streptococci,
anaerobes
Any bacterial growth is significant if the
specimen is collected from a normally-sterile
site (e.g., direct bladder puncture)
URINARY TRACT BACTERIOLOGY (2)
In pyelonephritis, the >10
5
cfu/ml rule
breaks down; fewer colonies can be
significant. Up to 20% of young women
with acute uncomplicated
pyelonephritis have between 10
3
and
10
4
cfu/ml. In catheterized patients in
whom specimens are obtained directly
from the catheter, between 10
2
and 10
4

cfu/ml should may be significant.
URINARY TRACT BACTERIOLOGY (3)
Patients with uncomplicated infection almost
invariably have a single organism; this is not
necessarily the case with complicated
infections
Unspun midstream urine: One
bacterium/high-powered field (hpf) correlates
with > 10
5
/ml (thus, high positive predictive
value)
URINARY TRACT BACTERIOLOGY (4)
Grams stain of spun urine: absence of
visible bacteria makes > 10
5
cfu/ml
highly unlikely (that is, high negative
predictive value)
20% of patients with urinary tract
infection do not have pyuria
ETIOLOGY OF COMMUNITY-ACQUIRED UTI
Aerobic gram-negative rods most
often
E. coli accounts for about 90%
Staphylococcus saprophyticus has
been increasingly appreciated in
recent years (with seasonality,
tending to occur in the summer)
Rare: anaerobes; pyogenic cocci;
viruses
ETIOLOGY OF NOSOCOMIAL UTI
E. coli is the most common pathogen
However, also common are other
Enterobacteriacae (Proteus, Klebsiella,
Enterobacter, Serratia, Providencia
species) and Pseudomonadaceae
(notably, Pseudomonas aeruginosa)
Enterococci: often in obstructive uropathy
Yeasts: Candida albicans, others
UREASE-PRODUCING MICROORGANISMS
Urease splits urea into ammonia, which has
a direct toxic effect on the kidney; inactivates
C4, and alkalinizes the urine with production
of struvite crystals (MgNH
4
P0
4
.6H
2
0) crystals
Proteus mirabilis most often; also
Providencia, Morganella, S. saprophyticus,
Klebsiella, Corynebacterium D2;
mycoplasma
Eradicate if at all possible
UTI IN ADULTS
Women: bacteriuria increases with age
and sexual activity
Men: bacteriuria is rare before age 50
(and as a corollary, calls for more
aggressive evaluation than in women).
Subsequently, bacteriuria increases with
onset of prostatism
ROLE OF BACTERIAL VIRULENCE IN UTI
Bacterial adherence to uroepithelial
cells involves specific binding of
bacterial surface receptors (adhesins)
to complementary components on the
epithelial cells (receptors).
The ability of E. coli to adhere to
uroepithelial cells is associated with
the presence of pili or fimbriae.
THE ROLE OF BACTERIAL VIRULENCE (2)
Specificity has been associated with the Gal-
alpha-->4-Gal specific adhesion localized at the
fimbrial polymer.
However, virulence of E. coli strains does not
seem to depend upon a single virulence factor.
There may well be an additive effect among
multiple virulence factors (including adhesins,
hemolysin, capsular polysaccharide,
aerobactin)

HOST DEFENSES:
ANTIBACTERIAL PROPERTIES OF URINE
Osmolality (extremes of high or low
osmolalities inhibit bacterial growth)
High urea concentration
High organic acid concentration
pH
HOST DEFENSES:
ANTI-ADHERENCE MECHANISMS
Bacterial interference (naturally
endogenous bacteria in the urethra,
vagina, and periurethral region)
Urinary oligosaccharides (have the
potential to detach epithelial-bound E.
coli
Tamm-Horsfall protein (uromucoid):
coating of E. coli by this protein might
prevent attachment
HOST DEFENSES:
MISCELLANEOUS
Mucopolysaccharide lining of the
bladder
Urinary immunoglobulins
Spontaneous exfoliation of uroepithelial
cells with bacterial detachment
Mechanical flushing of micturition
ROUTES OF URINARY TRACT INFECTION
Ascending infection is thought to be the
common route of nearly all forms of urinary
tract infection (bacteria initially colonize
periurethral tissues)
Descending (hematogenous) infection can
be important for a few organisms such as S.
aureus and Candida albicans, but in general
the kidney resists metastatic infection.
MECHANISMS OF LOWER UTI
Experimentally, 99.9% of a bladder
inoculum of bacteria is promptly
excreted by voiding.
Possible biologic explanations for the
frequency of UTI in some women
include: deficient antibodies in vaginal
secretions; and biochemical
differences in receptors on
uroepithelial cells.
MECHANISMS OF UPPER UTI
Ascent of bacteria from the bladder to
the kidneys is promoted by obstruction
and by reflux. In addition, motile
bacteria can ascend against the flow of
a column of urine. Gram-negative
bacteria (or endotoxin derived from
them) can inhibit ureteral peristalsis.
MECHANISMS OF UPPER UTI (2)
The renal medulla is an immunologic
desert. Its low pH (< 5. 5) and high
osmolality (which may reach 1300
mOsm/LK with a sodium of 425 mM and
urea of 850 mM) drastically interfere not
only with all aspects of leukocyte
function but also with antibody and
complement function.
LOCALIZATION OF UPPER VERSUS LOWER UTI
(2): IN PRACTICE
Frequency, dysuria, and urgency
(lower UTI symptoms) can occur with
upper UTI as well.
Fever and flank pain indicate acute
upper urinary tract infection.
Scarring of the kidney by imaging
procedures suggests chronic UTI.
The distinction is sometimes difficult.
SIGNS AND SYMPTOMS OF UTIS
Dysuria (burning pain upon urination)
Frequency
Urgency
Voiding in small amounts
Inability to void
Incomplete emptying of bladder
Low back / Suprapubic pain
ASSESSMENT FINDINGS IN UTIS
Hematuria (bloody
urine)
Cloudy urine
Flank pain
Abdominal pain
Fever

Nausea
Vomiting
URINALYSIS LABORATORY FINDINGS
Normal Findings
pH - 4.6 8.0
Appearance clear
Color pale yellow to amber
yellow
Odor aromatic
Specific Gravity 1.005
1.030
Protein - none
Glucose none
Ketones none
Blood none
Leukocyte esterase (WBCs)
none

pH Alkaline ( increases)
Appearance cloudy
Color - deep amber
Odor foul smelling
Specific Gravity may change
Protein maybe present
Glucose maybe present
Ketones - maybe present
Blood maybe present
Leukocyte esterase (WBCs)- present

URINALYSIS LABORATORY FINDINGS
MICROSCOPIC EXAMINATION
Normal Findings
Red Blood Cells
(RBCs) none
White Blood Cells
(WBCs) none
Casts none
Crystals none
Bacteria - none
Red Blood Cells
(RBCs) present
White Blood Cells
(WBCs) present
Casts none
Crystals present
Bacteria - present

SCREENING/DIAGNOSIS
1. ASB Dx based on results of a culture from clean-catch
specimen (* important to minimize contamination)
Women: bacteriuria = 2 consecutive voided urine samples
w/isolation of same strain in cfu/mL >100,000
Men: bacteria = single, clean-catch specimen with 1
bacterial species isolated in > 100,000 cfu/mL
Both: single catheterized urine specimen with 1 bacterial
species isolated in a count of > 1,000 cfu/mL


Infectious Disease Society of America:
Guidelines for Dx & Rx of ASB in adults
SCREENING/DIAGNOSIS
GUIDELINES, CONTINUED
2. Pyuria accompanying ASB not an indication for
antimicrobial Rx (A-2)
3. Pregnant women should be screened in early
pregnancy, at least once & treated if positive (A-1)
4. Screening of ASB & Rx if positive before these
urological procedures:
Transurethral resection of prostate (A3)
Procedures anticipated to cause possible mucosal
bleeding (A-3)


SCREENING/DIAGNOSIS
GUIDELINES, CONTINUED
5. No screening for ASB: (A-1 & A-2 strongly recommended via
research evidence)
Pre-menopausal, non-pregnant women (A-1)
Diabetic women (A-1)
Community older adults (A-2)
Institutionalized elderly (A-1)
Spinal cord injury (A-2)
Indwelling-catheterized patients (A-1)
6. Antimicrobial Rx of asymptomatic women with catheter-
acquired bacteriuria persisting 48 hrs after removed, should be
considered (B-1/good)
7. No screening or Rx of ASB renal transplant or solid organ
transplant recipients (C-3/weak)
Infectious Disease Society of America, 2005
Nicolle et al. 2005
www.guideline.gov/summary/summary

SCREENING/DIAGNOSIS
GUIDELINES, CONTINUED
Guide to Clinical Preventive Services, 2005
Similar consensus of IDSA recommendations
Clinical considerations
Dipstick analysis & direct microscopy have poor positive
& negative predictive value for detecting ASB
Urine culture = gold standard, but expensive for routine
screening in populations of low prevalence
New enzymatic urine screening test (Uriscreen
TM
)
showed 100% sensitivity & specificity of 81%
No clinical benefit to screen individuals other than
pregnant womendid not improve clinical outcomes.
Guide to Clinical Preventive Services, 2005
http://www.ahrq.gov/clinic/ppcletgp/geps2b.htm#bacteriaria


SCREENING & DIAGNOSIS
GUIDELINE CRITERIA FOR TREATMENT
The following are a recommended minimum set of criteria adapted from the McGeer (1991)
and Loeb et al. (2001) studies necessary to initiate diagnostics and AB Rx.

Indwelling catheter present:
two of the following must be met
Catheter is not present:
three of the following must be met

Fever (>38C/100.4F) or increase of 1.5C
(2.4F) above baseline temperature.
Chills
New costovertebral angle tenderness
New suprapubic pain, flank pain or
tenderness
Decreased mental or functional status
(delirium)
New-onset hematuria, foul-smelling urine,
or amount of sediment
Acute dysuria alone (key indicator) or fever
(>38C/100.4F) or increase of 1.5C (2.4F)
above baseline temperature
Chills
Frequency
Urgency
New costovertebral angle tenderness
Decreased mental or functional status (may be
new or increased incontinence related) *
New-onset hematuria, foul-smelling urine or (+)
sediment
New suprapubic pain, flank pain or tenderness

LABORATORY ANALYSIS
Dipstick Testing

Used in primary care & LTC settings. But for institutionalized adults, urinalysis
is preferable.

Chemically impregnated reagent strips (UA Chemstrip Screen) provide
preliminary/quick determinations of:

pH bilirubin
protein blood
glucose *nitrite
ketones *leukocyte esterase
urobilinogen specific gravity
Fischback, 2004
Fairly reliable, although U.S. Preventive Services Task Force (USPSTF)
report from research studies these have poor positive & negative
predictive value for detecting bacteriuria in asymptomatic patients.
www.ahrq.gov/clinic (2005)

LABORATORY ANALYSIS, CONTINUED
Routine UrinalysisKey Indicators of Infection
Urine collection 1
st
morning specimen is best
Straight catherization for those incontinent, functionally or cognitively
impaired
Specific gravity Measure of kidneys abiltiy to concentrte urine
Range of SG depends on state of hydration
Appearance Cloudy, may not indicate WBCs
Could indicate a change in urine pH causes precipitation
Alkaline urine phosphates cloudy
Acid urine urates cloudy
Color Pale yellow to amber
Variations can be caused by medications, disease processes (*nl urine
darkens on standing 30 min. after voidingoxidation of urobilinogen to
urobilin)
Odor nl faint odor when freshly voided
Foul-smellingoften presence of bacteria which splits urea to form
ammonia
Fischbach, 2004
LABORATORY ANALYSIS, CONTINUED
Routine Urinalysis, continued
pH Acid or basemeasures free H
+
ion concentration in urine 7.0neutral.
Indicates kidney function
Determines if systemic acid-base disorders of metabolic/resp. origin
control of pH manages bacteriuria, renal calculi & drug Rx
bacteria from a UTI produce alkaline urine
Blood or
Hemoglobin
Always an indicator of kidney/UT damage
Protein (Albumin) Single most important indication of renal disease
Microalbuminuria Below dipstick range of detection
Detects deteriorating renal function in diabetic patients (standard
screener)


Fischbach, 2004
LABORATORY ANALYSIS, CONTINUED
Routine Urinalysis, continued
*Nitrite (Bacteria)
Dipstick - rapid, indirect method to detect bacteria
common gram-negative organisms contain enzymes reduce nitrate
in urine to nitrite
some UTIs are caused by organisms that do not convert nitrate to
nitrite
(e.g., staphylococcus, streptococci)
*Leukocyte
Esterase
Esterase is released by leukocytes (WBCs) in urine
Microscopic exam & chemical test

__________
*U/A testing positive for nitrite & leukocyte esterase should be cultured for bacterial pathogen

Fischbach, 2004
URINE CULTURE AND SENSITIVITY
Traditional gold standard for significant bacteriuria
>100,000 cfu/mL of urine. Some argue criteria for
bacteriuria is only 100 cfu/mL of a uropathogen in
symptomatic females or 1,000 in symptomatic
males.

Bacterial identification from urine C&S, key in
males and females with complicated UTIs.
OTHER LABORATORY TESTS
Complete Blood Count with Differential
Indicated to R/O bacterial infection supports treatment
plan
Careful evaluation of WBC & differential (left shift)
Electrolytes
R/O dehydration & if IV fluids replacement needed
BUN, Creatinine
Determine renal function for nephrotoxic medications
Blood Culture
Identify bacteremic organism in suspected urosepsis
TREATMENT PLAN
Early detection/Rx goal is to prevent systemic infection,
bacteremia
Initiation of antibiotic treatment is recommended for a clinically-
diagnosed UTI. Adjust medication when urine C&S is final
Selection of antibiotic must be individualized and consider:
Side effect profile
Cost
Bacterial resistance
Likelihood of compliance (convenience, fewer pills/day s compliance)
Effect of impaired renal function on dosing
Possible adverse drug reactions in elderly (multiple drugs, co-
morbidities.
Osborne, 2004
Swart et al. 2004
TREATMENT PLAN
Recommended Treatment Regimens for Acute, Uncomplicated UTIs in the Elderly
Treatment Dosage/Duration Bacterial Coverage/
Resistance
Common Side
Effects
Compliance/
Convenience
Cost
I/E
Men Women
Sulfonamide
Trimethoprim-
Sulfamethoxazole
TMP-SMX
160/800 mg po bid x 3-14* days
*available in a syrup
If CrCl <15-30 mL/min, in half
(E. coli 20%)
resistance
Less effective
nausea, rash Fair/Good

longer duration of bid
compliance
I

Fluoroquinolones
Ciprofloxacin (2
nd
gen)

Levofloxacin (3
rd
gen)

100- 250 mg po bid x 3-14* days
If CrCL <30mL/min by half

250 mg po daily x 10 days
(complicated upper and lower UTI)
gram (-) effective
gram (+) only fair
headache, dizziness,
nausea, diarrhea
Good/Good
bid, longer duration
compliance
Excellent

E



Fosfomycin 3 g powder, dissolved in water
*single dose
gram (-) effective
gram (+) less effective
diarrhea, vaginitis,
nausea, rhinitis
Excellent VE, often
not on
formularies




Nitrofurantoin
(Macrobid)
100 mg po bid x 7 days
If CrCL <40 mL/min
not recommended
Narrow spectrum
gram (-) effective
gram (+) effective
nausea, vaginitis,
diarrhea
rate of severe
pulmonary &
hepatotoxicity
Fair
7-day regimen &
bid, compliance
I Prostatitis
NR


Miscellaneous
Beta Lactam ABs:
Cephalosporins (Cefuroxime, cefpodoxime)
Penicillins (ampicillin), Carbapenems (imipenem)
Phenazopyridine (Pyridium)not appropriate
for elderly or patients with renal insufficiency
resistance 2 Beta
Lactamase enzymes in
resistant bacteria
2
nd
/3
rd
gen Cephalosporins
>resistant to beta lactamase
PCN-anaphylaxis
Abdominal cramping
diarrhea
Fair for bid dosing I Prostatitis
NR


Data adapted from Swart et al. (2004), Osborne (2004), Wagenlehner et al. (2005), Mahan-Buttaro et al. (2006) and Evercare
Corp (2004)
I = inexpensive; E = expensive; VE = very expensive; NR = not recommended
*Longer duration for complicated UTI per individuals clinical status
TREATMENT PLAN
AB Rx for at least 10 days for institutionalized
elderly, as short-term therapy may not be as
effective.

Ten-14 days, if indicated, for complicated UTI.
(recommended for males)
Evercare, 2004

Conventional regimen of 7-10 days duration is
usually recommended.
Wagenlehner et al. 2005

TREATMENT PLAN
Complicated UTI
Can be common in LTC patients
Associated with azotemia, obstruction, or indwelling foley
Can lead to bacteremia, life-threatening systemic infection

Recommended Treatment for Acute Complicated UTI
IV antibiotic therapy--*consider renal & hepatic elimination,
creatinine clearance for dosage adjustment
3
rd
generation cephalosporin (Ceftriaxone = Rocephin) Rx 1 gram
IV every 24 hours
Or if fluoroquinolones (Levofloxacin = Levaquin) 250-500 mg IV
every 24 hours
Continue until afebrile, minimum of 48 hrs, then start oral therapy
and fluids x 14 days.
Mahan-Buttaro et al., 2006
E N D